Drug delivery through the skin is used in various applications in various forms due to its convenience of use. These drugs passing through the skin are mainly intended to be delivered to the systemic circulatory system, but some drugs such as those for treating atopy and cosmetics for skin whitening or wrinkle improvement, etc. are intended to be delivered to the skin itself. Despite this convenience and functionality, there are many problems in delivering drugs through the skin due to the intrinsic structure of the skin and it is not easy to develop the drugs passing through the skin. The horny layer of the skin consists of a brick structure composed of keratin-rich keratinocytes and a mortar structure composed of ceramides, fatty acids, waxes, etc. filled between the keratinocytes. Because these structures serve as a barrier, the skin has a very low penetrability to materials. Through diffusion, only small molecules with molecular weights of 500 Da or smaller can be delivered into the skin, and only materials having good lipophilicity can pass through the skin.
The release of a neurotransmitter occurs from a synaptic vesicle containing the neurotransmitter located at the nerve ending as the synaptic vesicle is fused with a presynaptic membrane and a passage is formed at the junction. The SNARE protein complex consisting of VAMP (vesicle-associated membrane protein, synaptobrevin), syntaxin 1a and SNAP-25 provides the force that is necessary for the fusion of the synaptic vesicle with the presynaptic membrane. The generation of the release passage of the neurotransmitter by the membrane fusion between the synaptic vesicle and the presynaptic membrane is a result of the action of the t-SNARE complex, which is a complex of the syntaxin 1a protein and the SNAP-25 protein associated with a target membrane, and the v-SNARE complex which is attached to the vesicle. Rearrangement of the lipid bilayer occurs during the membrane fusion. Because biological membranes repel each other strongly, the membranes cannot be fused spontaneously and, thus, a strong external force is required to overcome the repulsive force between the membranes. It is known that this force is provided by the SNARE protein. In other words, the formation of the SNARE complex is critical in exocytosis including the release of a neurotransmitter.
Recently, as it is known that plant-derived polyphenols exert functions similar to that of Botox by modulating the release of neurotransmitters, there have been efforts to use them in the form of applicable cosmetics or in situations where Botox cannot be used. However, because most polyphenols do not have good solubility, the amount that can be included in a cosmetic formulation is limited and, therefore, they are difficult to exhibit efficacy due to very low skin penetrability.
Meanwhile, calcium channel blockers are known to reduce muscle contraction by inhibiting the inflow of calcium, which plays an important role in muscle contraction, into muscle and vascular cells. Facial motion is achieved by contraction of the muscles lying under the skin. Different muscles are used to move different parts of the face.
For the calcium channel blocker to reduce muscle contraction and relax the muscle, the drug should be delivered to the muscular layer. However, it is not easy to deliver the drug to the muscular layer through simple application of cosmetics.
Transdermal injection of the calcium channel blocker may be limited for individuals because of pain. And, oral administration may cause side effects because it affects the whole body.
Although there have been efforts to deliver the calcium channel blocker to the skin by including in cosmetics for improvement of wrinkles and lines, improvement in skin penetration has not been achieved yet.